PHASE II CLINICAL STUDIES OF CHEMOPREVENTION AGENTS - WORKSTATEMENT 80: AN EX

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项工作的总体目标是确定免疫疗法是否可以解决轻度（宫颈）宫颈糜烂妇女的持续生殖器致癌HPV感染。 为此，该项目的短期目标是测试治疗性疫苗对使用巴氏试验证明低度细胞性宫颈炎的妇女中的生产性HPV 16型（HPV-16）感染的比较效力。 对于本研究，感兴趣的暴露是HPV-16 E7/HSP 65的三剂疗程 疫苗（由Stressgen Biotechnologies制造的HspE 7），其将具有免疫学和病理学意义的抗原（E7）与热休克蛋白偶联在一起，热休克蛋白是刺激巨噬细胞并促进细胞免疫应答的佐剂。 感兴趣的结果是从宫颈阴道区域清除病毒。 这是一项随机、安慰剂对照试验，受试者和研究者在研究期间对治疗分配均设盲。 简而言之，140名妇女，假设91%的留存率（即5%失访，4%方案违背失访），年龄在18 - 50岁之间，在巴氏试验中发现低度鳞状上皮内病变（LSIL）或意义不明的非典型鳞状细胞（ASCUS），HPV-16检测阳性，在前一年没有证实高级别SIL并且符合其他合格标准的患者将被随机接受疫苗或安慰剂，间隔一个月，分三次接种。 女性将在首次接种疫苗后20周和32周接受HPV-16检测。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this work is to determine whether an immunotherapy can resolve persistent genital oncogenic HPV infection in women who evidence mild (cervical) atypias. To this end, the short term goal of this project is to test the comparative efficacy of a therapeutic vaccine for productive HPV Type-16 (HPV-16) infection among women who evidence low-grade cellular atypias using Pap test. For this study, the exposure of interest is a three-dose course of HPV-16 E7/HSP65 vaccine (HspE7 made by Stressgen Biotechnologies), that couples together antigens that are immunologically and pathologically meaningful (E7) with heat shock protein, an adjuvant that stimulates macrophages and promotes cellular immune responses. The outcome of interest is viral clearance from the cervicovaginal area. This is a randomized, placebo-controlled trial where both subjects and the investigators will be blinded to treatment assignment for the duration of the study. Briefly, 140 women, assuming a 91% retention rate (i.e. 5% loss-to-follow-up, 4% loss-to-protocol-violation) who are 18 to 50 years old, who evidence low grade squamous intraepithelial lesions (LSIL) or atypical squamous cells of unknown significance (ASCUS) on Pap test, who test positive for HPV-16, who have not evidenced high grade SIL in the prior year and who meet other eligibility criteria will be randomized to receive vaccine or placebo in three doses, spaced one month apart. Women will be tested for the presence of HPV-16 at 20 and 32 weeks following their first vaccine dose.